Carbamylphosphate synthetase

Belkai d, M., Penverne, B., Denis, M., and Herve, G. (1987). In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 2. Reaction mechanism of aspartate transcarbamylase dissociated from carbamylphosphate synthetase by genetic alteration. Arch. Biochem,. Biophys., 254, 568-578. 

A defect in argininosuccinate synthetase coincides with markedly elevated citrulline values in the blood. Neither citrullinaemia nor a carbamylphosphate synthetase defect cause liver damage. By contrast, an argininosuc-cinase defect leads to microvesicular steatosis and megamitochondria with dilatation of the ER. 

The biomolecular modes of action of ornithine have been the subject of several experimental investigations. Ornithine activates the enzymes carbamylphosphate synthetase and ornithine carbamyl transferase, which are necessary for the liver-specific process of urea synthesis (133,139) this occurs mainly in the periportal hepa-tocytes (= definitive ammonia detoxification). Glutamine synthesis (binding of ammonia to glutamate) takes place predominantly in the perivenous hepatocytes (= transitory ammonia detoxification). Large amounts of glutamate are necessary for this. Aspartate, ornithine... 

Carbamylphosphate synthetase deficiency, ornithine transcarbamylase deficiency, and argininosuccinic acid synthetase deficiency Cystinosis Friedreich s ataxias Xerostomia and keratoconjunctivitis Myoclonus... 

Compensatory modulation Stimulation of carbamylphosphate synthetase by ornithine (3)... 

First three enzymes of the pyrimidine nucleotide pathway Carbamylphosphate synthetase aspartate transcarbamylase dihydro-orotase (Coleman et al., 1977)... 

Kerson, L. A., and Appel, S. H., 1968, Kinetic studies on rat liver carbamylphosphate synthetase, /. Biol. Chem. 243 4279. 

Tatibana, M., and Ito, K., 1967, Carbamylphosphate synthetase of the hematopoietic mouse spleen and the control of pyrimidine biosynthesis, Biochem. Biophys. Res. Commun. 26 221. 

The substrate structures and chemical reactions participating in the conversion of citrulline to arginine are given in Fig. 3. The intermediate formed in the conversion of ornithine to citrulline was found by Grisolia and Cohen in 1952. The structure of this compound was shown by chemical synthesis to be carbamylphosphate by Jones, Spector and Lipmann in 1955. Subsequent advances on carbamyl phosphate synthetase and ornithine transcarbamylase in the laboratories of P.P. Cohen, S. Grisolia, P. Reichard, M. E. Jones and M. Marshall have contributed to the enzymology and elucidation of the reaction mechanisms (cf. Fig. 3). The two enzymes are localized within the liver mitochondria, the last three enzymes of the cycle are in the cytosol. 

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